Addresses: *Vision Touch and Hearing Research Centre and Department
of Physiology and Pharmacology, ?Cognitive Psychophysiology
Laboratory, and ?Perception and Motor Systems Laboratory, The
University of Queensland, Brisbane, 4072, Australia.

Background: Over 200 years since the first reports of binocular
rivalry, Logothetis and his colleagues have challenged suggestions that
the phenomenon occurs early in the visual pathway. In alert monkeys, they
have shown that neurones in primary visual cortex (V1) continue to respond
to their preferred stimulus despite the monkey reporting its absence. Moreover,
they found that neural activity higher in the visual pathway is highly
correlated with the monkey's reported percept. These and other findings
suggest that the neural substrate of binocular rivalry must involve high
levels, perhaps the same levels involved in reversible figure alternations.

Results: We present evidence that activation or disruption of
a single hemisphere in human subjects affects the perceptual alternations
of binocular rivalry. Unilateral caloric vestibular stimulation changes
the ratio of time spent in each competing perceptual state. Transcranial
magnetic stimulation applied to one hemisphere disrupts normal perceptual
alternations when the stimulation is timed to occur at one phase of the
perceptual switch, but not at the other. Furthermore, activation of a single
hemisphere by caloric stimulation affects the perceptual alternations of
a reversible figure, the Necker cube.

Conclusions: Our findings suggest that interhemispheric switching
mediates perceptual rivalry. Thus competition for awareness in both binocular
rivalry and reversible figures occurs between, rather than within, each
hemisphere. This interhemispheric switch hypothesis has implications for
understanding the neural mechanisms of conscious experience and also has
clinical relevance since the rate of both types of perceptual rivalry is
slow in bipolar disorder (manic depression).

Background

Binocular rivalry refers to the alternating perceptual states that occur
when different images, such as orthogonal contours, are presented simultaneously,
one to each eye [1]. For each presented image, periods of perceptual dominance
alternate with periods of perceptual suppression, usually every few seconds.
Until recently, this phenomenon was thought to result from reciprocal inhibition
between monocular neurones (i.e. neurones responsive to input from only
one eye) in separate channels in primary visual cortex (V1) [2]. This model
of binocular rivalry however, has been challenged by the single-unit studies
of Leopold and Logothetis [3] which show that only a small percentage of
neurones in V1 exhibit activity that is correlated with a monkeyís
perceptual reports during rivalry. Moreover, of these neurones, all but
one were binocular (i.e. responsive to input from either eye). Sheinberg
and Logothetis have further demonstrated that high in the visual pathway,
in inferotemporal cortex and the superior temporal sulcus, around 90% of
neurones demonstrate activity that is correlated with the perception of
an effective visual stimulus [4; see reviews 5,6].

Psychophysical studies are also inconsistent with the monocular channel
competition model of binocular rivalry. Kovacs et al. [7] used a
patchwork rivalry paradigm in which one eye was presented with patches
of a monkey image interspersed with patches of a jungle scene, while the
other eye was presented with the opposite composite pattern. The observers
nevertheless reported alternations between the coherent monkey image and
the coherent jungle scene. This phenomenon was first demonstrated by Diaz-Caneja
in 1928 [8] whose finding was recently replicated and quantified [9]. Such
experiments show that the brain can organize aspects of each eyeís
presented image into rivalling coherent images. This synthetic capacity
during binocular rivalry cannot easily be explained in terms of reciprocal
inhibition between monocular channels.

Other psychophysical studies also support the notion that binocular
rivalry occurs between neural representations at a high level in the visual
pathway rather than between each eyeís presentation. Logothetis
et al. [10] rapidly swapped each eyeís presented image at
a rate of 3 Hz and demonstrated that this does not induce rapidly changing
perceptual alternations but rather, smooth and slow alternations indistinguishable
from normal rivalry. Moreover, the phenomenon of monocular rivalry [11-13]
is difficult to explain using monocular channel competition models. When
two differently coloured orthogonal gratings are superimposed in the same
eye, perception of each grating rivals in a manner similar to binocular
rivalry [11].

In accordance with these psychophysical and single-unit studies, two
recent fMRI studies of humans undergoing binocular rivalry have demonstrated
brain activation in regions of the visual processing hierarchy beyond V1
[14,15]. Similar high-level and widespread activation patterns during rivalry
were recently demonstrated using magnetoencephalography (MEG) [16]. While
it is important to understand at what level in the visual pathway binocular
rivalry is occurring, there is also a need for specific models of its neural
mechanism. It has been suggested that the perceptual alternations in binocular
rivalry and reversible figures such as the Necker cube, are the result
of modulation of visual processing regions by right-sided fronto-parietal
brain regions associated with selective attention and the generation of
behaviour [14,17]. This proposal is based on the finding of asymmetric
cortical activation in right fronto-parietal cortex during binocular rivalry
[14] and on current understanding of the functions of these regions [14,17].

Here we propose a hypothesis for the neural mechanism of perceptual
rivalry that extends this recent evidence that rivalry is a high-level
process. We suggest an interhemispheric switch model in which one cerebral
hemisphereís high-level visual processing regions adopt one of the
rivalling percepts while the other hemisphere adopts the other percept.
Competition for awareness during rivalry is therefore occurring between,
rather than within, each hemisphereís higher visual regions. This
interhemispheric switch hypothesis is based on a number of considerations.

Neuropsychological studies with normal and split-brain subjects support
the notions of hemispheric independence and dynamic modularity [18,19],
and patients who have had an entire hemisphere surgically removed can sustain
a coherent visual percept. The antithetical cognitive styles and moods
that have been linked to opposite hemispheric sites might require a mechanism
to alternate hemispheric activation [20,21]. Evidence for such hemispheric
alternations
in humans can be found in the literature on ultradian rhythms of cerebral
dominance [22] (but a periodicity in minutes-hours is indicated rather
than the seconds-long periods seen in binocular rivalry). Interhemispheric
switching is also evident in birdsong production [23]. Finally, a brainstem-mediated,
interhemispheric oculomotor alternation exists in fish [24] and may have
a counterpart in humans with damage to the cerebellum or brainstem [25].

To test our interhemispheric switch hypothesis of binocular rivalry,
we first examined the effect of caloric vestibular stimulation on the perception
of rivalling vertical and horizontal drifting gratings. PET [26] and fMRI
[27] studies have shown that caloric stimulation causes activation in contralateral
hemispheric structures that are known to be involved in attentional processing
[28] and binocular rivalry [14] (e.g. temporo-parietal, insular and anterior
cingulate cortex). In a clinical context, this technique can temporarily
ameliorate left-sided neglect and anosognosia (denial of disease) associated
with right hemisphere damage [20,29]. This ability of caloric stimulation
to unilaterally activate the same hemispheric structures implicated in
attentional processing and binocular rivalry suggests that, if rivalry
is mediated by interhemispheric switching, caloric stimulation should alter
the baseline perceptual predominance of one image relative to the other
(figure 1). Within-hemisphere competition at any level does not predict
an effect from such unilateral hemisphere activation.

Figure 1 Set-up for caloric stimulation and binocular rivalry
experiments and the effects on perceptual predominance predicted by the
interhemispheric switch hypothesis. (a) The rivalry set-up shows
a right-drifting vertical grating being presented to the left eye and an
upward-drifting horizontal grating being presented to the right eye using
liquid crystal shutters to restrict the presentation of each image to its
intended eye. The orthogonal gratings induce binocular rivalry and subjects
report their perceptual alternations using response keys on a keyboard.
The caloric stimulation procedure involves irrigating the external ear
canal with iced water until subjects report vertigo and examiners observe
nystagmus. The stimulation acts via the semicircular canals and brainstem
and results in activation of contralateral structures known to be involved
in attentional processing and binocular rivalry. (b,c) The expected
effects on rivalry alternations from unilateral hemisphere activation (according
to the interhemispheric switch hypothesis) are depicted by theoretical
frequency histograms. These represent the frequency (y-axis) of horizontal
and vertical perceptual intervals in seconds (x-axis) during the rivalry-viewing
period. In (b), there is no baseline predominance of either horizontal
or vertical percepts so unilateral hemisphere activation might be expected
to induce either a horizontal (bottom left) or vertical (bottom right)
predominance. In (c), there is a baseline predominance of the horizontal
percept that might be expected to disappear (bottom left), or even reverse
to a vertical predominance (bottom right) following unilateral hemisphere
activation by caloric stimulation. Actual rather than theoretical frequency
histograms are shown in figure 4.

We next tested predictions that binocular rivalry occurs at the same
level as reversible figures, by assessing the effect of caloric stimulation
during viewing of the Necker cube, a line diagram with ambiguous perspectives.
Similar effects of caloric stimulation on binocular rivalry and Necker
cube alternations would be further support for the notion that these phenomena
have a common neural mechanism [6,17,30]. If unilateral hemisphere activation
induces a change in the baseline predominance of either perspective of
the Necker cube, this would indicate that interhemispheric switching also
mediates the alternations of this bistable perceptual phenomenon.

Finally, since the longer time course of caloric stimulation in relation
to rivalry does not allow a direct assessment of the switching process
itself, we used unilateral single-pulse transcranial magnetic stimulation
(TMS), with its high temporal precision, to assess whether this could perturb
the rivalry process. The predictions for this experiment are: (i) disruption
of a hemisphereís designated percept (by TMS applied to temporo-parietal
cortex) would occur only if the TMS is applied during perceptual dominance
of that image; (ii) disruption of a hemisphereís designated image
should have little effect on perceptual alternations if the TMS is applied
when that image is perceptually suppressed (figure 2). Thus a phase-specific
pattern of interference effects is expected from unilateral TMS if binocular
rivalry is indeed an interhemispheric switching phenomenon.

Figure 2 Set-up for transcranial magnetic stimulation (TMS)
and binocular rivalry experiments and the perceptual interference effects
predicted by the interhemispheric switch hypothesis. (a) The circular
coil delivers a single pulse to the temporo-parietal region of the left
hemisphere. The subject views orthogonal stationary gratings (see methods
for details of the display used to avoid interaction with the intense magnetic
field) and reports their perceptual alternations using two response keys,
one of which triggers the magnetic stimulation. (b) The time course
of perceptual alternations shows the predicted disruptive effects of TMS
triggered by a switch to the horizontal percept. If the left hemisphere
adopts the horizontal percept, TMS applied to this hemisphere when the
horizontal image is perceptually dominant will disrupt this percept and
allow the vertical percept to assume dominance. The theoretical frequency
histogram (right) therefore depicts very short horizontal interval durations.
(c)
When the stimulation is delivered under identical conditions, but at the
opposite phase of the perceptual switch (i.e. triggered when the subject
reports a switch to vertical), disruption of the left hemisphere has little
effect since it is the right hemisphere that is responsible for the vertical
percept. Thus the theoretical frequency histogram(right)for this
contingency shows normal interval durations. Although not shown by theoretical
frequency histograms, it follows that if another subject shows shortened
vertical interval durations following left hemisphere TMS in one contingency,
and no effect in the other, this would indicate that the left hemisphere
has adopted the vertical rather than the horizontal percept. Actual rather
than theoretical frequency histograms are shown in figure 7.

Results

Binocular rivalry

The effect of caloric-induced left hemisphere activation on two subjectsí
rivalry alternations with drifting vertical and horizontal gratings is
demonstrated in figure 4 where it can be seen that the stimulation produces
a change in image predominance, reflected by the V/H ratio, the ratio of
total time spent perceiving the vertical and horizontal gratings, excluding
mixed percepts. In individuals, the effect ranged from strong to absent
(figure 5a,b), perhaps because of variation in the duration and efficacy
of the procedure. The group analysis compared the absolute magnitude of
change in the log-transformed V/H ratio between two pre-stimulation blocks
of rivalry (a measure of the random fluctuation in V/H ratio) with the
change between the block immediately prior to, and immediately following,
the stimulation (a measure of the experimental effect plus random variation).

The left hemisphere activation group demonstrated a statistically significant
greater change in the V/H ratio following stimulation than was observed
in baseline viewing (figure 5a,b). This effect had largely diminished by
the fifth block of rivalry (i.e. 10-20 minutes following stimulation).
Predominance comparisons were not significant for a control group of twelve
subjects who underwent the entire protocol minus the caloric stimulation
(figure 5a). Right hemisphere activation did not induce a change in image
predominance above baseline fluctuations (figure 5a).

Figure 3Analysis procedure for caloric stimulation experiments.
There are six blocks of rivalry each representing approximately seven minutes
of viewing. Each block contains four 100-second trials separated by 30-second
rest periods and each block is separated by a 2-minute rest period. The
first block is considered training and discarded before analysis. Blocks
2 and 3 are pre-stimulation blocks, while 4, 5 and 6 are post-stimulation
blocks. The predominance ratio is calculated by dividing the total time
spent perceiving the vertical gratings by the total time spent perceiving
the horizontal gratings, excluding mixed percepts. Similar ratios are calculated
for the oblique rivalry and Necker cube experiments. The ratios are log-transformed
before analysis. There is random variation in these predominance ratios
between two pre-stimulation blocks. Therefore, to show an effect of caloric
stimulation, there must be greater absolute magnitude of change in the
predominance ratio between blocks 3 and 4 (random variation plus experimental
effect) compared with the random variation seen between blocks 2 and 3.
Thus the graphs to the right in figure 5 show the ?D
log predominance? for blocks 2-3 and for blocks
3-4. Subtracting the predominance changes seen between blocks 2-3 from
those between blocks 3-4 removes the baseline noise and is labelled D
(?D log predominance?
) in the graphs to the left in figure 5.

As a control for possible effects on image predominance from ongoing,
undetected eye movements induced by the caloric stimulation, the experiments
were repeated with rivalling oblique gratings. Any effect from horizontal
eye movements would be spread equally across two orthogonal oblique gratings
and could not therefore affect image predominance. The results of these
experiments were the same as those for horizontal and vertical gratings.
Left hemisphere activation significantly changed predominance above baseline
fluctuations (figure 5c,d) and the effect had diminished by the fifth block
of rivalry. Right hemisphere activation again did not induce a significantly
greater change in predominance above baseline fluctuations, and the control
condition was also non-significant (figure 5c).

To assess the direction of change in image predominance following left
hemisphere activation, we looked at the twelve subjects with the largest
caloric-induced shifts. For horizontal and vertical rivalry, of the 12
leftmost subjects shown in red in figure 5a (excluding the first subject
who was left-handed), nine showed caloric-induced shifts towards perception
of the horizontal grating while three showed shifts favouring the vertical
grating. Similarly, in the oblique experiments, of the twelve subjects
showing the largest predominance shifts (the leftmost subjects in red in
figure 5c), nine favoured the rightward tilted (45°) grating, and three
favoured the leftward tilted (-45°) orientation. Summary statistics
for all caloric stimulation experiments are presented in table 1.

Figure 4Effects of caloric vestibular stimulation on two
individualsí perceptual alternations in binocular rivalry. In both
cases the predominance of one perceptual alternative is shifted by left
hemisphere activation (right ear cold caloric stimulation). These changes
are demonstrated in the frequency histograms of interval durations for
each rivalling image. The shifts are also reflected by the predominance
ratios shown in the top right hand corner of each of the histograms. (a,b)
This subject demonstrates a baseline horizontal predominance of V/H=0.93
which was increased to V/H=0.54 following caloric stimulation (which represents
a 3-4 ?D log predominance?
of 0.236). This was the usual direction of change for left hemisphere activation.
(c,d) The second subject also illustrates a post-stimulation change,
beginning with baseline horizontal predominance of V/H=0.94 which was reversed
to a vertical predominance of V/H=1.26 (representing a 3-4 ?D
log predominance? of 0.127). The direction of
shift for this subject occurred in only 3 of the 12 subjects with the most
marked predominance shifts, and suggests that designation of image to hemisphere
is not always fixed. The effect of caloric-induced unilateral (left) hemisphere
activation on the predominance of rivalling images supports the interhemispheric
switch hypothesis.

Necker cube

In the Necker cube experiments, the effect of left hemisphere activation
was dramatic in two subjects out of the 28. Each of the two subjects had
normal baseline perceptual alternations, but demonstrated a virtually complete
inability to see one of the two possible perspectives following caloric
stimulation. One of these subjects is illustrated in figure 6c. His post-stimulation
perception alternated between one clear perspective and the 'undecided'/indeterminate
option where no depth was perceived in the line diagram.

Other subjects showed predominance shifts following left hemisphere
activation (e.g. figure 6a,b) similar to, and generally more pronounced
than, the effect seen with binocular rivalry. The group analysis of these
remaining 26 subjects showed that left hemisphere activation caused a significant
change in perspective predominance greater than baseline fluctuations (figure
5e,f), and that the effect had diminished by the fifth block of data collection.
Both control and sham stimulation conditions were non-significant and right
hemisphere activation did not change Necker cube perspective predominance
above baseline fluctuations (figure 5e). Of the twelve subjects with the
largest predominance shifts, seven demonstrated shifts in predominance
towards one perspective while the remaining five subjects showed shifts
in the opposite direction.

Figure 5 The effect of caloric stimulation on perceptual alternations
during (a,b) binocular rivalry with drifting horizontal and vertical
gratings, (c,d) binocular rivalry with stationary oblique gratings,
and (e,f) viewingof the Necker cube. In all experiments,
activation of the left hemisphere significantly changed baseline perceptual
predominance of one image or perspective relative to the other (red inverted
triangles in figures on the left). The figures to the right demonstrate
the absolute magnitude of change in the log-transformed ratio of perceptual
predominance (i.e. ?D log predominance?
)between blocks 2-3 (baseline random fluctuation; pink triangles)
and between blocks 3-4 (experimental effect plus random fluctuation; purple
triangles) for left hemisphere activation. Each point along the x-axis
represents an individual subjectís data and subjects are ordered
according to the magnitude of the caloric effect. There is considerable
baseline noise but a majority of subjects show a shift in predominance
following left hemisphere activation in all experiments (see also table
1). Effects seem to be stronger with the Necker cube than with binocular
rivalry and three Necker subjects had such strong effects they could not
be shown on this graph (one is described in the legend box below 5e, and
for a description of the other two, see figure 6c). The figures to the
left show the data for left and right hemisphere activation and the control
condition that did not involve stimulation. Each point in these plots is
calculated by subtracting the predominance change between blocks 2-3 from
that between blocks 3-4 i.e. D (?D
log predominance? ). Thus points above the zero
line represent individuals who showed greater predominance change following
stimulation than in baseline viewing, while points below the zero line
indicate greater random change in predominance than that seen following
stimulation. The subjects are arranged in descending order of magnitude
and therefore, in the oblique rivalry and Necker cube experiments, the
data point for an individual subject in one group does not necessarily
correspond to the same subjectís data in the other two groups.

Figure 6The effect of caloric vestibular stimulation on perceptual
alternations of a reversible figure, the Necker cube. (a,b) Left
hemisphere activation (right ear caloric stimulation) shifts a baseline
perspective predominance (A=lower square face closer to observer; B=upper
square face closer to observer; ratio calculated as for binocular rivalry
and excludes indeterminate percepts) of A/B=1.3 to A/B=0.85. This represents
a 3-4 ?D log predominance?
of 0.185. Overall, subjects demonstrated shifts in both directions following
stimulation, indicating that, unlike for binocular rivalry, designation
of perceptual configuration to hemisphere may be arbitrary. Also shown
(c) are the raw time series data for a single subject demonstrating
the normal baseline perceptual alternations, with roughly equal time spent
experiencing each perspective, followed by the effect of caloric stimulation
which virtually eliminated the ability to perceive one of the two perspectives.
The subject alternated between perspective A and the ëundecidedí
response option (where no depth was perceived in the line diagram) following
left hemisphere activation. This more dramatic effect may be related to
the fact that this subject received prolonged iced water irrigation compared
with other subjects. The same effect was seen in one other subject, so
the effects of caloric stimulation on the predominance of Necker cube perspectives
vary from infinity (2 subjects) to the more graded effects seen in the
26 subjects shown in figure 5e,f. The effect of unilateral (left) hemisphere
activation on Necker cube alternations is further evidence that binocular
rivalry and reversible figures have a common neural mechanism and suggests
to us that this mechanism is interhemispheric switching.

Transcranial magnetic stimulation

Since left hemisphere activation showed a clear effect on both rivalry
and reversible figure alternations, we concentrated on this hemisphere
for the TMS experiments. Figure 7 shows that application of a TMS pulse
to the temporo-parietal region of the left hemisphere had a disruptive
effect on binocular rivalry which was, as predicted, phase-specific. TMS
applied just as the percept was switching from vertical to horizontal caused
a reversion to vertical indicated by shortened horizontal interval durations,
but there was no disruptive effect when the TMS pulse was timed to occur
at the opposite perceptual switch. The data for all subjects are shown
in table 2 where it can be seen that this pattern occurred in three subjects.
In two other subjects, TMS delivered on a switch from horizontal to vertical
caused a reversion to horizontal indicated by shortened vertical interval
durations, but there was no similar perceptual disruption when TMS was
delivered on a switch to horizontal in these same subjects. Clear phase-specific
disruptive effects of TMS thus occurred in five out of the seven subjects
we tested, despite the difficulties associated with simultaneously establishing
a threshold stimulation intensity and an optimal location.

Figure 7The effect of left hemisphere transcranial magnetic
stimulation on a single subject's binocular rivalry alternations (subject
1 in table 2). There is a marked disruption of percepts when left hemisphere
TMS is contingent on one direction of perceptual switch but not when the
contingency is at the opposite phase. (a) Control session with no
TMS. (b) TMS delivered when the subject signalled a switch from
the vertical to the horizontal percept, caused an immediate reversion to
the vertical percept, indicated by a dramatic shortening of the horizontal
interval durations. (c) TMS administered at the opposite phase (when
the subject signalled a switch from the horizontal to the vertical percept),
did not cause perceptual disruption. Such phase-specific disruption effects
occurred in five of the seven subjects we tested (see table 2). This result
supports the interhemispheric switch hypothesis and cannot be explained
using a within-hemisphere competition model.

Discussion

Interhemispheric switching mediates perceptual rivalry

Our results demonstrate that unilateral (left) hemisphere activation
by caloric stimulation influences the alternation patterns of binocular
rivalry with drifting vertical and horizontal gratings and with stationary
oblique gratings. A change in the perceptual predominance of the rivalling
images following unilateral hemispheric activation, is predicted by the
interhemispheric switch hypothesis of binocular rivalry and is not explicable
by models based on within-hemisphere competition. This interhemispheric
switch hypothesis is consistent with suggestions that it is the stimulus
representations rather than the eyes that rival during binocular rivalry
[7-13] and that rivalry is occurring high in the visual pathway [3-17].

In further support of an interhemispheric switch model of binocular
rivalry we have demonstrated a phase-specific disruptive effect of unilateral
(left) transcranial magnetic stimulation on perceptual alternations. One
stimulation contingency caused perceptual disruption while stimulation
at the opposite phase had little effect even though delivered under identical
conditions. These results cannot be explained by within-hemisphere models
but are predicted by the hypothesis proposed in the present paper.

A similar effect of caloric-induced left hemisphere activation on the
predominance of perceived perspectives of the Necker cube was demonstrated
and supports the notion of a common neural mechanism for both binocular
rivalry and reversible figures. The data presented here can be explained
if both types of perceptual rivalry are mediated by an interhemispheric
switch mechanism. Thus we suggest that in perceptual rivalry, each hemisphere
adopts one image or perspective, and perceptual alternations reflect hemispheric
alternations and thus competition between the hemispheres for visual awareness.

The lack of a change in predominance above baseline fluctuations for
the right hemisphere activation group, in all three caloric stimulation
experiments, may be explained in the following way. A recent fMRI study
of humans undergoing binocular rivalry found a right-sided fronto-parietal
activation asymmetry [14]. This study did not separately analyze regional
activation for each of the two perceptual states and hence could not assess
the interhemispheric switch hypothesis. However, since activation patterns
were assessed by combining both directions of perceptual switch, the finding
of asymmetric activation in right fronto-parietal cortex suggests that
these regions are involved in gating perceptual alternations or selecting
the neuronal representations for access to visual awareness [14]. This
notion is supported by reports that right-sided frontal lesions cause the
perception of only one of the two possibilities in reversible figures [31].
The finding of right fronto-parietal activation during perceptual rivalry
also emphasizes that regions involved in the gating or selection process
may be functionally quite distinct from the visual regions responsible
for the alternative image representations [14,17]. Left ear cold caloric
stimulation might activate both the control and the visual regions in the
right hemisphere and this dual activation may be responsible for the lack
of predominance change in this group.

The directions of shifts in predominance induced by left hemisphere
activation also raise interesting issues. There appears to be a predilection
for the horizontal grating to be adopted by the left hemisphere although
this was not always the case. The direction of predominance change in the
oblique rivalry experiment was also biased, towards the right-tilted (45°
) orientation. It is interesting to note that both the horizontal grating
and the right-tilted oblique grating were presented to the right eye. Thus
eye-of-presentation may influence which hemisphere adopts which image.
This is consistent with evidence that there is a higher proportion of binocular
neurones with a dominant input from the contralateral eye [32]. However,
since an individualís predominance does not completely reverse in
preliminary experiments in which the eye-of-presentation has been reversed,
we cannot yet rule out some combination of eye-of-origin and higher-order
effects. Thus the horizontal grating may often be adopted by the left hemisphere
due to a cultural bias for horizontal scripts and the left-lateralization
of sentence reading [33]. The direction of predominance shifts for the
Necker cube experiments suggest that with these stimuli (which do not involve
separate presentation to the eyes) there may be an arbitrary designation
of perspective to hemisphere. Future experiments might repeat stimulation
in the same subject to elucidate whether the designation of image or perspective
to hemisphere, is fixed or varies within an individual.

Table 2Individual subject data demonstrate the phase-specific
effect of TMS during binocular rivalry. The bolded median interval durations,
all less than 1 second, show perceptual disruption of the interval immediately
following TMS (Hsand Vs;compare
these intervals with the same subjectís control intervals). Note
that subjects 1-3 have perceptual disruption of the horizontal intervals
when TMS is triggered by a switch to horizontal, but no perceptual disruption
when TMS is triggered by a switch to vertical (see also figure 7). Subjects
4 and 5 on the other hand, experience perceptual disruption when TMS is
triggered on a switch to vertical but no disruption when TMS is triggered
at the opposite phase. This suggests that subjects 1-3 have the horizontal
percept in their left hemisphere while subjects 4 and 5 have the vertical
percept in this hemisphere. Despite this difference, subjects 1-5 demonstrate
phase-specific effects of TMS and thus support the interhemispheric switch
hypothesis. The statistical test compares the number of horizontal and
vertical intervals less than 1-second duration in each of the two stimulation
contingencies. Binomial expansions [42] were calculated to establish the
probability of obtaining the observed distributions through chance.

Hemifields and hemispheres

In thinking about our model of interhemispheric switching, it is important
not to be limited by spatially-symmetric notions of hemifield representations
in V1. It has been suggested that the coherence rivalry demonstrated by
Diaz-Caneja [8,9] rules out the possibility that rivalry occurs between
each cerebral hemisphere [6]. However the 1.5-degree stimulus used in the
rivalry experiments reported here produces bilateral activation even in
V1 (where binocular overlap is around one degree in the foveal region of
higher primates) and in MT (where overlap is around 5 degrees). Moreover,
the Diaz-Caneja experiment says nothing about interhemispheric competition
at higher processing levels. The binocular neurones in inferotemporal cortex
whose activity correlates with monkeysí reported percepts [4], can
process information presented to either hemifield as indicated by
their properties of bilateral receptive fields and ipsilateral field loss
following section of the posterior corpus callosum and anterior commissure
[34].

Thus rivalry between the hemispheres at a level beyond V1 is compatible
with Diaz-Canejaís results and may actually help to explain the
phenomenon of coherence rivalry. Diaz-Canejaís experiments [8,9]
and the patchwork experiments of Kovacs et al. [10], suggest that
the brain is able to group or bind coherent image segments irrespective
of their eye-of-origin. How might the brain achieve such reorganization
of presented image components into rivalling coherent images? The interhemispheric
switch model suggests that the brain groups or binds the segments of each
coherent image in separate hemispheres. Thus the perceptual resources of
each hemisphere may be independently and alternately employed to achieve
this kind of synthetic ability.

Eye movements

In the horizontal and vertical rivalry experiment, despite the care
we took to delay post-stimulation testing until nystagmus had ceased, it
is at least possible that the observed predominance shifts actually result
from ongoing, undetected horizontal nystagmus that acts to reduce the spatial
frequency and contrast of the vertical grating. The fact that three subjects
had increased predominance of the vertical grating after caloric stimulation
makes this explanation unlikely. Moreover, the results of the oblique rivalry
experiment strongly argue against this interpretation. Results for the
Necker cube experiments are also difficult to explain by eye movements.
Finally, in the TMS experiments, the stimulation was delivered under exactly
the same conditions for both stimulation contingencies, and any effect
due to eye movements should therefore be seen in both contingencies. This
was clearly not the case, as illustrated in figure 7.

Brainstem oscillator or corpus callosum?

The highly-developed corpus callosum connecting the human hemispheres
may immediately suggest itself for a key role in the proposed interhemispheric
switch. We think that this is unlikely and predict that split-brain subjects
would still experience perceptual alternations. We suggest that the primary
mechanism of interhemispheric switching involves different subcortical
bistable oscillator circuits related either to the short-period perceptual
alternations studied here or to long-period alternating hemispheric activity
[21,22]. The suggestion that a subcortical bistable oscillator mediates
interhemispheric switching is based on both comparative considerations
and clinical evidence in humans.

Bistable oscillators are well-studied in invertebrates [35] and interhemispheric
switching has been observed in the brains of birds [23] and fish [24] that
lack a corpus callosum. Moreover, in human patients with midline cerebellar
or brainstem damage, a roughly 90-second oscillator has been described
that shows side-to-side alternation of eye movements [25]. This oculomotor
alternation, known as periodic alternating nystagmus, is believed to be
a brainstem phenomenon and is accompanied by perceptual alternations during
binocular rivalry consistent with our proposals concerning interhemispheric
switching (Miller and Pettigrew, in preparation).

The role of the brainstem in mediating synchronous neural activity [36]
will be particularly interesting if temporal correlation [37] of neurones
with similar preferred stimuli is shown to be important at high levels
of the visual pathway during binocular rivalry. A brainstem oscillator
might increase response synchronization of neurones with similar preferred
stimuli in one hemisphere, before switching its output to the opposite
hemisphere to bind neurones preferring the other image. Thus simultaneous
bilateral recordings from single neurones and pairs of neurones high in
the visual cortex during rivalry in alert monkeys would enable testing
of the interhemispheric switch hypothesis through analysis of both the
rate and temporal correlation of neural activity. Other means of verifying
the hypothesis include looking for the presence of alternating patterns
of cerebral activation (and coherence) with electroencephalography, MEG
or fMRI. It will be necessary for such studies to analyze signals derived
while one percept is dominant separately from those generated during its
suppression.

Conclusions

We have presented a readily testable neurophysiological model of binocular
rivalry and reversible figure alternations based on the perceptual interference
effects we have observed following unilateral hemisphere activation and
disruption. Our results suggest that during perceptual rivalry, each hemisphere
adopts one of the competing images or perspectives, and perceptual alternations
correspond to hemispheric alternations. The interhemispheric switch hypothesis
has clinical relevance because of the findings that patients with bipolar
disorder (manic depression) have a slow switch rate for both binocular
rivalry [21] and reversible figures [38]. Our model may therefore offer
a link between such findings and the emerging picture of hemispheric asymmetries
in the generation and treatment of mood disorders [reviewed in 21; and
see 39-41]. Finally, the hypothesis of interhemispheric switching raises
new issues for the scientific study of consciousness. At any one time during
perceptual rivalry, the perceived visual scene may depend on neural activity
in only one hemisphereís higher visual regions.

Materials and Methods

Horizontal and vertical binocular rivalry: Eighteen right-handed
and two left-handed, male and female subjects ranging from 18 to 54 years
of age underwent cold caloric stimulation of the right ear (left hemisphere).
Fourteen right-handed male and female subjects of similar age had left
ear (right hemisphere) stimulation. Twelve control subjects underwent the
full protocol minus the stimulation. Written, informed consent was obtained
according to a protocol approved by the University of Queensland's Medical
Research Ethics Committee. A VisionWorks&trade; display with liquid
crystal shutters was used to present an upward-drifting horizontal (square-wave)
grating to the right eye while simultaneously presenting a right-drifting
vertical grating to the left eye (figure 1). The liquid crystal shutters
allow the fields of view for each eye to be superimposed, with both horizontal
and vertical targets occupying the same spatial location, so no training
in fixation was required.

The stimuli were presented in a circular patch and subtended 1.5°
of visual angle with a spatial frequency of 8c/deg moving at 4c/sec. Contrast
of the gratings was 0.9. Subjects sat three metres from the monochrome
computer monitor (green, P46 phosphor, persistence=500ns) and recorded
their perceptual alternations by pressing one of three keyboard response
buttons for vertical, horizontal or mixed percepts. The latter were removed
before analysis. Baseline perceptual alternations were recorded for half
an hour. This was followed by the caloric stimulation (or a rest period
in the control group) and a further half-hour of rivalry data was then
collected. Each half-hour session was divided into three blocks, consisting
of four 100-second trials. Each trial was separated by a 30-second rest
period, and each block by a two-minute rest period. The first block was
considered training and was discarded before analysis.

Oblique binocular rivalry: Twenty right-handed males aged 18-25
were tested on three separate occasions. Each session involved half an
hour of baseline rivalry viewing and was then followed by: (i) five minutes
rest, (ii) right ear caloric stimulation and, (iii) left ear caloric stimulation.
The two caloric sessions were counterbalanced. A further half-hour of rivalry
data was then collected. The set-up was the same as for the horizontal
and vertical rivalry experiments. A rightward tilted (45°) grating
was presented to the right eye and a leftward tilted (-45°) grating
to the left eye. The stimulus characteristics were otherwise the same as
for the horizontal and vertical gratings except that the oblique gratings
were stationary.

Necker cube: Twenty-eight right-handed males aged 18-25, underwent
control sessions and left hemisphere activation by right ear caloric stimulation.
Two of the left hemisphere activation subjects were unable to see one of
the two possible perspectives following stimulation. Their extreme results
meant that they were not included in the subsequent group analysis even
though they offer striking support for the interhemispheric switch hypothesis.
Sixteen subjects also underwent right hemisphere activation by left ear
caloric stimulation while the remaining ten subjects underwent sham caloric
stimulation with body-temperature water (and thus no vestibular stimulation).
Following control sessions, the order of subsequent sessions was counterbalanced.
The Necker cube was presented on a matt white surface 100cm from the subject
and at eye level. The cube subtended 7.6°
x 7.4° (height x width) of visual angle
and had a central fixation cross (0.5° x
0.5° ). Subjects were asked to maintain
gaze on the fixation point and to record their perceptual alternations
using a keyboard with a response key for each of the percepts and a third
option for ëundecidedí or indeterminate percepts or if their
gaze strayed from the fixation point. The latter were removed before analysis.
Alternations were recorded for half an hour, divided into three blocks
each with three 100-second trials. Each trial was separated by a 60-second
break, and each block by a 4.5-minute break. Subjects then had (i) five
minutes rest (control), (ii) sham stimulation using water at body temperature,
or (iii) cold caloric stimulation of the right or left ear. A further half-hour
of data was then collected.

Caloric stimulation: Cold (iced) water irrigation was administered
by a medical practitioner using a 50ml syringe and soft silastic tubing
from a butterfly cannula. Head position was 30 degrees from horizontal
bringing the lateral semicircular canal into the vertical plane; the mid-sagittal
plane was vertical. The tubing was inserted into the external auditory
canal until it was adjacent to the tympanum. Iced water was then instilled
until the subject reported vertigo and the examiner observed nystagmus
(usually following 10-30ml of iced water irrigation). Subjects demonstrated
nystagmus with the brisk phase in the direction contralateral to the ear
stimulated. We did not have good control over the duration or the intensity
of the procedure because of the pain and nausea that the experimenter was
reluctant to prolong. All subjects have been included in the results irrespective
of the judged efficacy of the procedure. Post-stimulation data collection
began when all visible signs of nystagmus and subjective vertigo had ceased.
Sham caloric stimulation was administered by irrigation with water at body
temperature.

Transcranial magnetic stimulation: Single pulse TMS was applied
to the left temporo-parietal cortex using a 90mm circular coil (Magstim
200&trade;, The Magstim Company). The centre of the coil was positioned
approximately 13cm from the nasion and 12cm from the mid-sagittal line
and oriented to induce current flow in a posterio-anterior direction in
the temporo-parietal cortex. The coil itself was held firmly against the
scalp by one of the experimenters, while the feeder cables connecting the
main stimulator to the coil were supported by an overhead gantry. Magnetic
stimuli were triggered when the subject signalled a perceptual switch either
to the vertical percept, in one trial, or to the horizontal percept in
the other. The intensity of stimulation was varied between 0.66 and 1.1
T according to the subject. The rivalry apparatus used in these experiments
consisted of two 1cm (diameter) by 2cm translucent plastic tubes each with
a 50d lens at the proximal end, viewing a 1mm (diameter) square wave grating
(8 cycles) on translucent paper at the distal end (see figure 2). The tubes
were positioned by the subject on the face-plate of a safety mask so that
the gratings viewed by each eye were orthogonal in orientation and viewed
at the same location.

Acknowledgements: This work was supported by the National Health
and Medical Research Council of Australia and the Australian Research Council.
We thank Andrew Tilley for helpful discussions and especially thank all
subjects for their participation.